Numerous changes in properties of the cell surface have been associated with important developmental and neoplastic phenomena such as cellular adhesion, growth regulation, tissue invasion, metastasis, and escape from the host immune response. By using defined components, our studies using model membranes demonstrate that a specific cell surface molecule is responsible for causing altered membrane function and hence altered cellular social behavior. The formation of two spherical model membranes at the tips of two syringes has allowed us to study the role of gangliosides in membrane adhesion and look for changes in conductance between two such membranes during the process of adhesion. The membranes are formed in aqueous 100 mM NaCl, 10 mM KC1, 1 mM CaC12 from 1% (w/v) egg phosphatidylcholine in n-decane, with or without mixed beef brain gangliosides. After thinning to the "black" bilayer state, two membranes were moved into contact. Membranes made without gangliosides were found to adhere. The contact area increased linearly with time over a 5-\to 20-min period. The rate of increase was less as the ganglioside concentration increased up to 8.5 mole-percent which produced no adhesion. The electrical conductance of individual membranes made without gangliosides was 39 plus or minus 11 nS/cm2. The inclusion of gangliosides reduced the conductance 20-fold to 2.2 plus or minus 0.7 nS/cm2. However, at neutral pH, when two membranes containing gangliosides adhered, the conductance between them increased in concert with adhesion. The region of adhesion had a specific conductance three times that of the nonadhering regions of membranes. The role of electrostatic bridging by calcium was investigated. In the absence of calcium or in the presence of 2 mM EDTA, adhesion proceeded after a longer lag time at about one-half the normal rate. Membrane fusion during adhesion is unlikely because: (1)\the adhesion process can be reversed by physically moving one membrane away from the other and (2)\two different fluorescent probes do not mix across the junction. These data suggest that mixed gangliosides inhibit membrane adhesion, and by exclusion from the adhesion zone, they allow an increase in conductance. (A)